Dietary sodium depletion in man is followed by rapid conservation of sodium by the kidneys. The rapidity of the response suggests that the gastrointestinal tract is involved in the early recognition of changes of sodium load presented to the body and in the regulation of sodium excretion. In a pilot study to test this hypothesis in man, normal volunteer subjects were placed on a sodium deficient diet for five days at which time sodium balance was achieved. When the subjects were subsequently repleted with an oral sodium load, they excreted more sodium than when they received the same sodium load intravenously. The differences were statistically significant at eifht, twelve and twenty-four hours after sodium repletion. This constitutes evidence that there is a receptor mechanism for sodium in the gastrointestinal tract which regulates urinary sodium excretion. The proposed work is intended to develop this concept in studies to establish an experimental animal model, determine the specificity of the sodium receptor, its anatomic site in the gastro-intestinal tract, the physiologic mechanism by which it regulates sodium excretion, and its role in the pathogenesis of edema-forming states associated with gastrointestinal disease. These studies will involve normal human volunteers and volunteer patients, experimental animals, and laboratory methods such as urinary electrolytes, creatinine and aldosterone measurements.